Predictive Factors and Clinical Outcome of Viral Breakthrough during Lamivudine Treatment for Chronic Hepatitis B Infection

Park, Neung Hwa; Shin, Jung Woo; Park, Jong Ho; Bang, Sung Jo; Kim, Dae Hyun; Joo, Kwang Ro; Kim, Do Ha

Abstract

BACKGROUND/AIMS: Long-term treatment with lamivudine causes breakthrough, but the clinical course after lamivudine breakthrough is not well known. The aims of this study were to evaluate the clinical course in lamivudine after breakthrough, and to identify predictive factors of breakthrough. METHODS: 124 patients with chronic hepatitis B infection, who represented viral breakthrough during lamivudine therapy, were included. The mean duration of lamivudine therapy and additional lamivudine therapy after breakthrough was 30.5 months and 12.5 months, respectively. RESULTS: The cumulative breakthrough rates at 12, 18, 24 and 36 months were 8, 24, 36 and 52%, respectively. After viral breakthrough, only 4 patients maintained normal ALT levels. 120 patients showed ALT elevation. The number of patients with ALT levels greater than 5 times, and greater than 10 times, the upper normal limit were 67 (56%) and 29 (24%), respectively. While still on lamivudine therapy after breakthrough, 98 patients presented ALT elevation. Only 22 had normalized ALT levels. Hepatic decompensation developed in 2 patients. HBeAg seroconversion after breakthrough occurred in 10 patients. The changing pattern of quantitative HBeAg levels during lamivudine therapy was the only predictive factor associated with viral breakthrough. The mean time of turning points in decrescendo-crescendo patterns of HBeAg levels during lamivudine therapy was earlier than viral breakthrough (9 months vs. 17 months). CONCLUSIONS: These results suggested that deterioration of hepatic function can usually be observed after breakthrough. The serial monitoring of serum quantitative HBeAg levels may allow an early recognition of viral breakthrough.